Malignant non-Hodgkin Lymphoma Research Articles

Mit der HIV-Infektion assoziierte maligne Lymphome

The course of disease in 119 HIV-infected patients (117 men, 2 women; median age 38.5 years) with malignant tumours other than Kaposi's sarcoma was analyzed in a multi-centre retrospective study. This was conducted to obtain initial information concerning the incidence, clinical features and results of therapy in HIV-associated neoplasms, especially malignant lymphomas. The most frequent tumour was malignant non-Hodgkin's lymphoma (98 patients, 82.5%), seven patients had Hodgkin's disease, five had solid tumours, four a polyclonal lymphoproliferative syndrome, three an acute lymphocytic leukaemia, and two had other lymphoproliferative diseases. 58% of the non-Hodgkin's lymphomas occurred in patients with marked immunodeficiency, 85% were high grade malignancies and 47% had primary extranodal disease. 56% of primary nodal lymphomas also had visceral spread (Stage IV). Lymphoblastic non-Hodgkin's lymphoma was more common in patients with favourable immunological status, presented less frequently with primary extranodal disease, was diagnosed earlier than other non-Hodgkin's lymphomas, and appeared to carry a better prognosis. 78 out of the 98 patients with non-Hodgkin's lymphoma had been treated, 66 with cytotoxics. The median survival time was 6 months. Longer remission periods, of at least 12 months, were seen in ten of the 78 patients (13%). Despite the overall poor prognosis and the pre-existing immune defect, palliative (chemo-)therapeutic measures are both justified and promising, and may also result in life-prolonging remissions.

Size of cell nuclei in non-Hodgkin lymphomas. Prognostic and diagnostic significance

Morphometric analysis of cell-nucleus size was undertaken in 300 cases of malignant non-Hodgkin lymphomas. The results were compared with histological findings and survival time. It was found that the histological lymphoma groups differ significantly only occasionally with regard to nucleus size. Within the groups the values have such wide scatter that in the individual case it is not possible to assign it on morphometric data. This scatter mirrors the difficulties encountered in histological classification which - as the objective data indicate - are due to numerous transitions between different types of lymphoma. Analysis of survival data shows that nucleus size is of considerable prognostic value, if certain exceptions such as lymphoblastic lymphoma are taken into account. The results favour tripartite division of malignant lymphomas for prognostic purposes.

Komplikationen im Verlauf eines Muckle-Wells-Syndroms

A 35-year-old woman had since early childhood suffered from recurrent urticaria-like rash, intermittent fever, arthralgia and pancochlear inner-ear deafness. At the age of 17 years she also developed a steroid-resistant nephrotic syndrome, found to be due to renal amyloidosis (type AA). The triad of renal amyloidosis, inner-ear deafness and recurrent urticaria is characteristic of Muckle-Wells syndrome, which has a hereditary basis. Rapidly progressive renal failure necessitated long-term haemodialysis and two renal transplantations. The accompanying immunosuppressive treatment with corticosteroids, azathioprin and, later, cyclophosphamide brought about a remission of the joint and skin abnormalities. After removal of the first donor kidney and termination of immunosuppressive treatment the syndrome recurred with subacute growth of an amyloid goitre as well as amyloidosis of the optic nerve. A few weeks before death a malignant non-Hodgkin lymphoma of the stomach was demonstrated. It was presumably a complication of long-term immunosuppression and not of the Muckle-Wells syndrome. The patient died of the complications of combination chemotherapy. Necropsy revealed generalized amyloidosis.

HIV-assoziierte Lymphome

Forty-one HIV-positive homosexual men (mean age 39.8 [23-72] years) with malignant lymphomas were examined with the object of exploring the clinical and pathological spectrum of HIV-associated lymphomas in Central Europe, and their therapeutic aspects. There were 33 patients with non-Hodgkin lymphoma of high malignancy and four with non-Hodgkin lymphoma of low malignancy; four further patients suffered from Hodgkin's disease. 27 patients died during the period of observation. The mean survival period after diagnosis was 5.5 months. It depended on the stage reached by the lymphoma at the time of diagnosis: 11.8 months in stage I, 10.6 months in stage II, 7 months in stage III, 3.3 months in stage IV and 1.3 months in patients with primary involvement of the central nervous system by the lymphoma. Eight out of nine patients with highly malignant non-Hodgkin lymphoma in stage I or II attained complete and lasting remissions after chemotherapy or irradiation. However, only minimal prolongation of life was achieved in the 16 patients with lymphomas in stages III or IV. The response rate among all patients treated (complete and partial remissions) was 75%; 45% achieved complete remission. Hodgkin's disease responded well to standard therapy, but the disease rapidly recurred in every case.

Syndrome de la queue de cheval révélant un lymphome malin non hodgkinien vertébral

Malignant non-Hodgkin lymphoma is a lymphoid proliferation. Peripheral neuropathies are observed in only 2-8% of cases. We report a case in which cauda equina syndrome in a 29-year-old man led to the diagnosis of a painless non-Hodgkin lymphoma of the spine. Combined chemotherapy and radiation therapy produced spectacular improvement. Infiltration of the cauda equina roots is rare in malignant non-Hodgkin lymphoma and raises problems for positive diagnosis. The good outcome under treatment underlines the interest in considering this cause in disorders affecting the cauda equina, despite its rarity.

B-Cell Lymphoma of the Mandible: A Case Report

The mandible is an infrequent localisation of primary osseous non-Hodgkin's lymphomas. Few cases of mandibular non-Hodgkin's lymphomas (NHL) have been reported. A rare condition of primary malignant non-Hodgkin's lymphoma of the mandible in 53-year-old man, was reported at the Department of Maxillofacial and Plastic Surgery in Charles Nicolle Hospital (Tunis, Tunisia). Histologic and Immunohistochemical (IHC) examination Confirmed a B-Cell lymphoma. The purpose of this report is to describe this rare case of NHL of the mandible, explore the diagnosis and workup, and discuss treatment strategies. In this localisation, neither the clinical features nor the radiologic appearances are often pathognomonic. Particular care must be taken to consider lymphoma in the differential diagnosis because this uncommon lesion can pose significant diagnostic problems and is frequently misdiagnosed.

Paraneoplastische Limbische Enzephalitis als Erstmanifestation eines malignen Non Hodgkin Lymphoms

Paraneoplastic limbic encephalitis (PLE) is a rare disease that is probably caused by an immunological reaction against CNS-structures. It may present with neurological, neuropsychological or psychiatric symptoms. Besides treatment of the underlying neoplastic disease, there is no generally applicable evidence-based treatment. PLE is most frequently associated with certain carcinomas, but its occurrence with Hodgkin lymphoma has also been recognized. Association with non-Hodgkin lymphoma has only been occasionally reported in single cases. We report two additional patients, in whom malignant non-Hodgkin lymphomas of the B- and T-cell lines were detected. Treatment with corticosteroids in one and chemotherapy in the other case were associated with clinical improvement.

Outcomes and Prognostic Factors in Primary Intraocular Lymphoma: A Multicenter Rare Cancer Network Study

Primary intraocular lymphoma (PIOL) is a very rare, malignant non-Hodgkin's lymphoma, representing a subset of primary central nervous system lymphoma (PCNSL). Its natural history and outcome are generally thought to be quite different and worse than that of intraorbital lymphoma (Martinet et al, IJROBP, 2003), but this is based on very small series or case reports. The goal of this study was to assess the clinical profile, treatment outcome, and prognostic factors in patients with PIOL treated with radiation therapy and/or chemotherapy.

Cryptococcose neuroméningée chez un patient traité pour un lymphome non Hodgkinien

Introduction HIV infection remains the main underlying disease for meningeal cryptococcosis. Other diseases may be associated to this infection such as non-Hodgkin's lymphoma. Case report We report a case of cryptococcal meningitis in a 46-year-old man treated for malignant non-Hodgkin's lymphoma and considered on remission for three years.Treatment with amphotericin B failed and the patient died. Conclusion The poor prognosis of cryptococcal meningitis in patients with malignancies such as lymphoma requires early diagnosis to improve prognosis.

P002 Quality of life in patients with Hodgkins and non-Hodgkins malignant lymphoma and multiple myeloma treated by means of autologous haematopoietic stem cell transplantation: an effect of selected demographic, psychosocial and health aspects on quality of life

P002 Quality of life in patients with Hodgkins and non-Hodgkins malignant lymphoma and multiple myeloma treated by means of autologous haematopoietic stem cell transplantation: an effect of selected demographic, psychosocial and health aspects on quality of life

Somatically mutated immunoglobulin VH genes without intraclonal heterogeneity indicate a post germinal center origin of primary intraocular diffuse large B-cell lymphomas

8072 Background: Primary intraocular lymphoma (PIOL) is a very rare high grade malignant non-Hodgkin lymphoma, usually of the diffuse large B cell lymphoma (DLBCL) type, which presents in the vitreous, retina and/or the optic nerve. Sixty to 80% of patients with PIOL eventually disseminate to the brain, whereas up to 15% of primary central nervous system lymphoma (PCNSL) patients exhibit ocular involvement. For these reasons, PIOL is regarded as a subtype of PCNSL. Analysis of the immunoglobulin heavy chain (VH) sequences in PCNSL tumors demonstrated biased overrepresentation of the VH4–34 gene and indicated derivation of these tumors from highly mutated germinal center (GC) B cells with ongoing mutational activity. Whether PIOL tumors are of similar or different origin is presently unknown. Methods: Immunoglobulin VH genes were examined in vitrectomy specimens of 4 PIOL patients, 1 patient with concomitant PCNSL and 1 patient with systemic DLBCL involving the eye. The extracted DNA was amplified by PCR using VH family specific primers, cloned and sequenced. Results: Seven clonal VH rearrangements belonging to the VH4, VH3 and VH1 families were cloned from the analyzed cases. In concordance with previous reports, the lymphomatous eye infiltrate from the PCNSL patient revealed a mutated clonal VH4–34 gene with intraclonal heterogeneity -a manifestation of active ongoing mutational activity. All the PIOL clonal VH rearrangements also exhibited mutated sequences with homology to the germline sequences ranging between 76 to 95%. However, in contrast to PCNSL, 3 out of 4 PIOL cases exhibited no intraclonal heterogeneity while the remaining case demonstrated ongoing somatic mutations in one of the 2 clonal VH rearrangements detected in this tumor. Interestingly, the clinical course of this patient was highly unusual, since he exhibited systemic dissemination during follow-up. Conclusions: Analysis of VH gene sequences from PIOL tumors indicate a post- GC derivation and suggest that they belong to the activated B cell (ABC)-like subtype of DLBCL. This is in contrast to the GC-origin of closely related PCNSL. No significant financial relationships to disclose.

Treatment of Benign Orbital Pseudolymphomas With the Monoclonal Anti-CD20 Antibody Rituximab

To report the results of treating patients with orbital pseudolymphomas with the anti-CD20 monoclonal antibody rituximab. Patients were included in the study if they had an orbital mass and biopsy-proven orbital pseudolymphomas between January 1, 1998, and December 31, 2005. The study focused on patients treated with rituximab. Ninety-eight patients were evaluated, and the biopsy results revealed malignant non-Hodgkin lymphoma in 72 (73%); the other 26 (27%) had a pseudolymphoma. Eleven (42%) of the 26 patients with a pseudolymphoma were treated with rituximab, 375 mg/m2, intravenously each week for 4 doses, and 10 (91%) of the 11 responded. Seven patients were either treated with maintenance rituximab or successfully retreated with rituximab after relapse. None of the 10 responders has become refractory to rituximab. Benign lymphoproliferative tumors are responsive to monoclonal antibody therapy targeted to B lymphocytes. Rituximab should be considered a treatment option for orbital pseudolymphomas.

Diagnosis and management of neoplastic lesions of the submandibular triangle

Review of submandibular triangle neoplasms (benign and malignant) treated at a tertiary referral centre in the United Kingdom (1986-2004). One hundred and seven cases identified via computerised search of histopathology records over the 18 year review period. Retrospective review clinical notes and collation with data maintained prospectively by the senior author. Forty nine benign and 58 malignant neoplasms of the submandibular triangle were reviewed. Definitive diagnosis was by excision and pathological examination. Pleomorphic adenoma (n=37) were the most common benign neoplasms. For malignant lesions (n=58), 48 were primary malignancies and 10 metastatic lesions. The most frequent primary lesions were malignant non-Hodgkin lymphoma (n=22), adenoid cystic carcinoma (n=9) and mucoepidermoid carcinoma (n=9). The mainstay treatment for both benign and malignant lesions was surgical either by extracapsular excision of the gland/lesion or selective levels I, IIa and III neck dissection. The main post-operative complication was temporary weakness of the marginal mandibular nerve (13%). Submandibular triangle neoplasms are rare and pose many diagnostic and therapeutic challenges. There is a relatively high incidence of malignant neoplasms in this region (54%). Benign tumours manifest a mild course of disease and have an excellent prognosis following adequate excision. Malignant tumours have a poor symptomatology that can result in late (often post-operative) diagnosis. The adequacy of primary surgery is crucial and would support the approach of a more radical excision primarily with a selective levels I, IIa and III neck dissection; ensuring a definitive operation for benign lesions, avoiding the risks of tumour spillage associated with a more limited excision; and removing the primary echelon of lymph nodes at risk of metastasis if the pathology in fact turns out to be malignant; without a significantly higher morbidity in comparison with an extracapsular gland/lesion excision.

Malignant non-Hodgkin's lymphoma developing late after pneumonectomy

A 64-year-old man underwent a left pneumonectomy for a benign bronchial stenosis in 1968. In 1997, a left parietal thoracic tumour: T-type malignant non-Hodgkin's lymphoma (MNHL) was detected. It was treated by chemotherapy and radiation therapy. After 6 years follow-up, the patient is alive and in remission. We have found only one case of such a lymphoma in the literature. It could be classified as pyothorax-associated lymphoma from which there are several published cases especially in Japanese literature.

Humoral response to hemagglutinin components of influenza vaccine in patients with non-Hodgkin malignant lymphoma

Lymphoma disease and immunosuppressive drugs used in this case cause immunity disorders increasing the risk of severe infections, including influenza. There are opinions that patients from high-risk group are not able to respond to vaccination effectively and vaccination may contribute to exacerbation of the chronic disease. The aim was to assess humoral response to influenza vaccine in 32 patients with non-Hodgkin malignant lymphoma (mean age 57.2) and 32 healthy subjects (mean age 44.3). Sixteen patients were treated with immunosupressive drugs (group A) and 11 were not subjected to this therapy (group B). Levels of antihemagglutinin (anti-HA) antibodies were assessed in sera before vaccination and after 1 month by hemagglutination inhibition test. Nasal and throat swabs were collected from persons with influenza symptoms during the study to detect the etiological agent of the infection. Post-vaccination anti-HA antibody levels were significantly higher than pre-vaccination values and mean fold increases (MFI) ranged from 9.3 to 12.2 in patients and from 27.6 to 44.3 in healthy subjects. The percentage of patients with the protective anti-HA antibody titers ≥1:40 (protection rate) ranged after vaccination from 59.4% to 68.8%. The percentage of patients with at least a four-fold increase of anti-HA antibody titers (response rate) after vaccination ranged from 46.9% to 68.8%. There were no significant differences in antibody levels between patients treated with immunosuppressive drugs and those not treated. No respiratory infections were laboratory confirmed. This study showed that influenza vaccine is less immunogenic in patients with non-Hodgkin malignant lymphoma, because it induces antibody production in lower titers in comparison to the production in healthy people. Despite this, influenza vaccine should be offered to this group, considering high MFI values and response rates as well as the protective effect for individual patients.

Phase III Intergroup Study of Fludarabine Phosphate Compared With Cyclophosphamide, Vincristine, and Prednisone Chemotherapy in Newly Diagnosed Patients With Stage III and IV Low-Grade Malignant Non-Hodgkin's Lymphoma

To compare the efficacy and safety of fludarabine phosphate with cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated, advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase III, multicenter study. Between 1993 and 1997, patients were randomly assigned to treatment with either fludarabine (25 mg/m2 intravenously [IV] daily for 5 days every 4 weeks) or CVP (cyclophosphamide 750 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 1; and prednisone, 40 mg/m2 orally on days 1 through 5 every 4 weeks). Results Overall response (OR) rates were significantly improved in the fludarabine arm versus the CVP arm, both for the intent-to-treat (ITT) population and assessable patients (P < .001). Complete response (CR) rates in the ITT population were also higher after fludarabine treatment. The CR rate was 38.6% for fludarabine compared with 15.0% for CVP. There were no statistically significant differences in time to progression (TTP), time to treatment failure (TTF), and overall survival (OS) between treatment groups. WHO grades 3 and 4 hematologic adverse events were more common in the fludarabine arm. However, concerning the higher incidence of granulocytopenia, this did not translate to more infections in fludarabine-treated patients. Newly diagnosed lgNHL patients who received fludarabine achieved higher OR and CR rates compared with CVP-treated patients. No differences in TTP, TTF, and OS were noted. Fludarabine is a highly active single agent in lgNHL. Combination therapies incorporating fludarabine are now being further evaluated as first-line therapy in follicular NHL.

Primary Cranial Vault Lymphoma Presenting As a Traumatic Subdural Hematoma

The authors present a rare case of a primary cranial vault lymphoma, mimicking a subacute subdural hematoma after head trauma. A 78-year-old woman was admitted to the hospital with progressive left hemiparesis, headache and a gradually increasing soft lump over the right parietal region 1 week after head trauma due to falling from a high place. A computed tomography (CT) scan demonstrated a hyperdense parieto-occipital subdural and subgaleal lesion together with marked midline shift and white matter edema. Considering her trauma story and clinical progression, the patient underwent an emergency operation with the diagnosis of subdural hematoma. However, the lesion was found to be of a tumors nature and the histopathological diagnosis was high-grade malignant non-Hodgkin's lymphoma. The authors emphasize the rarity of primary cranial vault lymphoma and its importance in the differential diagnosis of cranial vault mass lesions extending either intra- or extracranially. This case may be considered as another example where magnetic resonance imaging (MRI) is the ultimate definitive test in the emergency ward whenever CT demonstrates any findings which are unclear.

Fine-needle aspiration cytology combined with flow cytometry immunophenotyping is a rapid and accurate approach for the evaluation of suspicious superficial lymphoid lesions

The authors report a prospective study on 88 samples of superficial lesions (lymph nodes, skin nodules, and breast tumors), performed by fine-needle aspiration cytology (FNAC) in 74 patients, allowing (i) morphologic analysis combined with immunophenotyping by flow cytometry (FCM) and (ii) a cytogenetic study in 33 cases. Thirty-nine FNAC (44.3%) were performed at the time of diagnosis. The cytology results were correlated with histopathologic examination in 32 cases. Forty-nine FNAC (55.7%) were performed in the context of follow-up of a lymphoma and the results were correlated with those of histopathologic examination in 14 cases. In this study, the concordance between FNAC plus FCM and histopathologic examination was 90% for low-grade non-Hodgkin's malignant lymphomas (NHLs) and 83% for high-grade NHL. The limits of this morphologic and phenotypic approach are (i) partial tumor infiltrations, (ii) Hodgkin lymphoma, and (iii) T-cell NHL. In conclusion, it may be said that this combined approach is very useful for diagnosis and follow-up of patients but requires teams experienced in the sampling technique and the morphologic diagnosis of the various types of low-grade NHL in which supplementary ancillary studies may be performed when morphology and flow cytometry immunophenoyping are not conclusive.

Nasopharyngeal lymphoid hyperplasia after therapy for childhood lymphomas

Although diffuse thymic hyperplasia after therapy has been reported in lymphomas, no report is found in the medical literature about hyperplasia of other lymphoid tissues following chemotherapy in malignancies as far as we could reach. So, we planned to investigate the nasopharyngeal region of the lymphoma cases during their follow-up while at remission. Children who were in follow-up after cessation of oncological therapy with the diagnosis of lymphoma were evaluated for their nasopharyngeal lymphoid tissues by means of computed tomography. When a mass lesion was diagnosed, biopsies were taken. Among 23 lymphoma cases in follow-up, at a median of eight months (range 1–13 months), eight patients (six Hodgkin's and two Non-Hodgkin's malignant lymphoma) developed nasopharyngeal lymphoid hyperplasia (34.78%) that were proven to be benign by means of biopsies. Two of the patients also developed thymic hyperplasia. Nasopharyngeal hyperplasia regressed in four patients at a median of four months. Nasopharyngeal lymphoid hyperplasia may be diagnosed after the cessation of therapy in lymphomas and whatever the cause, it seems to be a benign process.

Rituximab Enhances Radiation-Triggered Apoptosis in Non-Hodgkin's Lymphoma Cells Via Caspase-dependent and - Independent Mechanisms

Rituximab (RTX), a chimeric human anti-CD20 monoclonal antibody, is currently employed in the treatment of malignant non-Hodgkin's lymphoma (NHL) either alone or in combination with other cytotoxic approaches. The present study examines the effects of ionizing radiation in combination with RTX on proliferation and apoptosis development in B-lymphoma RL and Raji cells. RTX was used at a concentration of 10 microg/mL 24 hours prior to irradiation at a single dose of 9 Gy. CD20 expression, cell viability, apoptosis, mitochondrial membrane potential and apoptosis-related proteins were evaluated in the treated B cells. The constitutive level of CD20 expression in RL and Raji lymphoma cells did not play an essential role in RTX-induced cell growth delay. Both lymphoma cells showed similar inhibition of cell proliferation without apoptosis development in response to RTX treatment. Exposure to ionizing radiation induced cell growth delay and apoptosis in RL cells, whereas Raji cells showed moderate radio-resistance and activation of cell growth at 24 hours after irradiation, which was accompanied by increased radiation-triggered CD20 expression. The simultaneous exposure of lymphoma cells to ionizing radiation and RTX abrogated radioresistance of Raji cells and significantly enhanced cell growth delay and apoptosis in RL cells. X-linked inhibitor of apoptosis protein (XIAP) and the inducible form of heat shock protein 70 (Hsp70) were positively modulated by RTX in combination with ionizing radiation in order to induce apoptosis. Furthermore, it was demonstrated that mitochondrial membrane potential dissipation is not an essential component to induce apoptosis-inducing factor (AIF) maturation and apoptosis. Our results show that RTX-triggered enhancement of radiation-induced apoptosis and cell growth delay is achieved by modulation of proteins involved in programmed cell death.